Preliminary experiments using squid giant axons show that if these are injected with aequorin and then depolarized with high concentrations of K in seawater, the Ca entry that is measured as an increase in aequorin glow is virtually totally dependent upon Nai. These findings suggest two points: (a) that Na/Ca exchange is the principal method whereby Ca enters with depolarization and (b) that the Na/Ca exchange system is electrogenic and hence responds to membrane depolarization by increasing Ca influx and decreasing Ca efflux. A second set of preliminary observations showed squid giant axons are microinjected with phenol red, and when the absorption peaks of this dye are measured in a rotating wheel spectrophotometer, it is possible to make measurements of pHi with substantially more sensitivity and better time resolution than can be obtained with a glass microelectrode, which is also used in these measurements. If the squid axon is repetetively stimulated it can be shown that the axoplasm becomes acidified and that upon cessation of stimulation, there is a very slow recovery of pHi. The acidification can also be observed if the fiber is depolarized with high (K) seawater and in both instances acidification is totally dependent on the presence of Ca in the seawater. It is concluded that Ca entry which leads to a buffering of the (Ca)i also leads to the release of H ion and this phenomenon is to be studied as the means of getting at Ca movement in axoplasm where other methods might not be easy to apply. THIS YEAR'S GOALS: Make detailed measurements of pH change as a function of Ca entry; attempt to divide this into a metabolically sensitive and insensitive fraction; make measurements of pH change in extruded axoplasm as a function of Ca addition; make voltage clamp measurements of the current of Na/Ca exchange.